Detection of nucleic acids, proteins, and small molecules is helpful for complete patient analysis. For example, nucleic acid sensors are useful for the detection of many biological markers of disease, protein detection identifies a host response, and small molecule detection profiles metabolites. Although fluorescence-based nucleic acid hybridization arrays have proven useful for high-throughput screening applications, they have not shown utility for bench-top clinical diagnostics. Electrochemical assays based on charge are well suited for point-of-care applications mostly because charge detection requires only simple electrode instrumentation and does not require stringent procedures to report on mutations, protein binding, as well as other perturbations.
In conventional analytical platforms, electrochemical readout occurs at the surface onto which the substrate monolayers are assembled. As a result, these conventional assays report on bulk changes that occur over the entire electrode area. Multiplexing has enabled multiple experimental conditions to be run in parallel, however, these multiplex platforms still yield only average changes that occur over the entire surface. Comparing individual electrodes can be misleading, as small variations can lead to substantial differences in electrochemical responses.
Electrochemical methods are low cost, portable, and require only modest instrumentation. Electrochemistry has been used to detect nucleic acids with high sensitivity and without the need for polymerase amplification, however facile analysis and detection of multiple substrates in the presence of protein analytes has remained challenging.